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Pasi Antero Jänne
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Lunch & Poster Display session (ID 58)
- Event: ELCC 2019
- Type: Poster Display session
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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122P - Osimertinib as first-line (1L) treatment for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC): Final efficacy and safety results from two phase I expansion cohorts (ID 404)
12:30 - 13:00 | Author(s): Pasi Antero Jänne
- Abstract
Background
Osimertinib is a 3rd-generation, CNS-active EGFR-tyrosine kinase inhibitor (TKI) that potently and selectively inhibits both EGFR-TKI sensitising (EGFRm) and EGFR T790M resistance mutations. Earlier results from the Ph I AURA (NCT01802632) and Ph III FLAURA (NCT02296125) studies have established 1L osimertinib efficacy. We report final efficacy and safety data from two Ph I expansion cohorts who received 1L osimertinib 80 or 160 mg for advanced EGFRm NSCLC in AURA.
a9ded1e5ce5d75814730bb4caaf49419 Methods
Treatment-naïve pts with locally advanced/metastatic EGFRm NSCLC received osimertinib 80 or 160 mg once daily. Endpoints included objective response rate (ORR), progression-free survival (PFS) and safety evaluation. EGFRm status was confirmed via local and/or central laboratory testing. Key eligibility criteria included measurable disease and WHO performance status 0/1. Pts with stable asymptomatic CNS metastases were eligible. Data cutoff: 1 May 2018.
20c51b5f4e9aeb5334c90ff072e6f928 Results
Overall, 60 patients (pts) were enrolled at two doses (80 mg, n = 30; 160 mg, n = 30): 75% female; 72% Asian; 43% with EGFR ex19del; 48% with L858R. Five pts were EGFR T790M mutation-positive by central test at study entry. Median follow up: 19.1 mo. ORR (95% CI): 67% (47, 83) in the 80 mg cohort, 87% (69, 96) in the 160 mg cohort, 77% (64, 87) overall. Median duration of response (95% CI): 19.3 mo (12.2, 24.7) in the 80 mg cohort, 16.7 mo (9.7, 29.0) in the 160 mg cohort, 18.0 mo (12.5, 24.7) overall. Median PFS (95% CI): 22.1 mo (12.3, 30.2) in the 80 mg cohort, 19.3 mo (11.1, 26.0) in the 160 mg cohort, 20.5 mo (13.7, 26.1) overall (78% maturity). 42% (95% CI 29, 54) and 14% (95% CI 6, 26) of pts were progression free at 24 and 48 mo, respectively. Dose reductions occurred in 27% and 60% of pts at 80 mg and 160 mg, respectively. Most common adverse events overall: (% [Grade ≥3]) diarrhoea (80 mg, 63% [3%]; 160 mg, 87% [7%]), stomatitis (80 mg, 47% [0]; 160 mg, 53% [3%]), paronychia (80 mg, 37% [0]; 160 mg, 57% [10%]).
fd69c5cf902969e6fb71d043085ddee6 Conclusions
Consistent with previously reported results, 1L osimertinib for EGFRm advanced NSCLC results in prolonged PFS at both doses and better tolerability at the 80 mg dose.
b651e8a99c4375feb982b7c2cad376e9 Clinical trial identification
NCT01802632 (25 February 2013).
7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement
Medical writing support was provided by Natasha Cary BSc, from iMed Comms, an Ashfield Company and funded by AstraZeneca.
934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study
AstraZeneca.
213f68309caaa4ccc14d5f99789640ad Funding
AstraZeneca.
682889d0a1d3b50267a69346a750433d Disclosure
J.C-H. Yang: Honoraria: BI, Roche, MSD, AstraZeneca, Novartis; Consulting/advisory: BI, Novartis, AstraZeneca, Roche/Genentech, Clovis Oncology, Lilly, MSD, Merck Serono, Celgene, Astellas Pharma, Bayer, Pfizer, Ono Pharmaceutical, Bristol-Myers Squibb, Yuhan, Hansoh. S.S. Ramalingam: Advisory boards: AbbVie, Amgen, AstraZeneca, BMS, Celgene, Genentech, Lilly, Merck, Roche, Nektar, Loxo, Takeda; Research grants: Merck, Tesaro. C.K. Lee: Advisory boards: AstraZeneca, Roche, Norvatis, Pfizer. Research funding to institution: AstraZeneca for the trials in which I am currently involved. T. Kurata: Research grants: AstraZeneca, MSD; Honoraria: AstraZeneca, MSD, Ono, Bristol-Myers Squibb, Chugai, Eli Lilly. D-W. Kim: Advisory board membership, personal expenses: Novartis. T. John: Consultancy: AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Takeda, Pfizer, Novartis, Merck, Roche. N. Nogami: Honoraria: AstraZeneca, Chugai Pharmaceutical, Eli Lilly Japan K.K., MSD, ONO Pharmaceutical, Pfizer Japan Inc., Taiho Pharmaceutical. Y. Ohe: Honoraria, consulting, research funding: AstraZeneca, Chugai, Dainippon Lilly, Ono, BMS Japan, Daiichi Sankyo, BI, Bayer, Ignyta, Pfizer, MSD, Taiho, Novartis, Kyorin, Kyowa Hakko Kirin, Takeda, Celltrion. Y. Rukazenkov: Employee and shareholder: AstraZeneca. P.A. Jänne: Consultancy: AstraZeneca, BI, Pfizer, Merrimack, Roche/Genentech, Chugai, AceaBiosciences, ARIAD Pharma, Ignyta, LOXO Oncology; Stock ownership: Gatekeeper Pharma; Research funding: Astellas, AstraZeneca; IP: EGFR mutations licensed to Lab Corp. All other authors have declared no conflicts of interest.
cffcb1a185b2d7d5c44e9dc785b6bb25 -
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183TiP - A phase II study of [fam-] trastuzumab deruxtecan (DS-8201a) in HER2-overexpressing or -mutated advanced non-small cell lung cancer (ID 475)
12:30 - 13:00 | Author(s): Pasi Antero Jänne
- Abstract
Background
Approximately 30% of non-small-cell lung cancers (NSCLC) are human epidermal growth factor receptor 2 (HER2)-overexpressing (immunohistochemistry [IHC] 2+ or 3+) and approximately 2% have HER2-activating mutations. However, no HER2-targeted therapies are approved for the treatment of NSCLC. [Fam-] trastuzumab deruxtecan (DS-8201a) is a novel HER2-targeted antibody-drug conjugate with a humanized HER2 antibody, a topoisomerase I inhibitor payload, cleavable peptide-based linker, and a high drug-to-antibody ratio of 7 to 8. In an ongoing phase 1 trial, [fam-] trastuzumab deruxtecan (6.4 mg/kg) had a confirmed objective response rate (ORR) of 58.8% (10/17) in HER2-expressing or -mutated NSCLC and 72.7% (8/11) in HER2-mutated NSCLC, with a manageable safety profile (Tsurutani et al, WCLC 2018).
a9ded1e5ce5d75814730bb4caaf49419 Trial design
This multicenter, open-label, 2-cohort, phase 2 study will assess the efficacy and safety of [fam-] trastuzumab deruxtecan (6.4 mg/kg once every 3 weeks) in HER2-overexpressing or -mutated unresectable and/or metastatic nonsquamous NSCLC that is relapsed/refractory to standard treatment or for which no standard treatment is available (NCT03505710). Approximately 80 subjects will be enrolled; 40 in each of 2 cohorts (cohort 1: HER2-overexpressing [IHC 3+ or IHC 2+]; cohort 2: HER2-mutated including exon 20 insertions and single-nucleotide variants in kinase, transmembrane, and extracellular domains [eg, L755S, V659E, S310F]). To be eligible for cohort 1, HER2-overexpression must be assessed and confirmed by central testing based on archival samples. To be eligible for cohort 2, any HER2-activating mutation must be documented based on archival tumor samples. Study treatment will be continued until progressive disease or unacceptable toxicity. The primary endpoint is ORR based on RECIST version 1.1 by an independent radiologic facility. Secondary efficacy endpoints include progression-free survival, duration of response, disease control rate, and overall survival. Safety assessments include serious and treatment-emergent adverse events. The study will enroll subjects in North America, Europe, and Japan. Recruitment began in May, 2018.
d9b324a48b043b3d87bc9b3fe620f260 Clinical trial identification
NCT03505710.
7a6a3ffa2dadc03a6151ee2c4d6fa383 Editorial acknowledgement
Editorial assistance was provided by Stefan Kolata, PhD, of AlphaBioCom, LLC.
934ce5ff971f1ab29e840a35e3ca96e9 Legal entity responsible for the study
Daiichi Sankyo, Inc.
213f68309caaa4ccc14d5f99789640ad Funding
Daiichi Sankyo, Inc.
682889d0a1d3b50267a69346a750433d Disclosure
D. Planchard: Member on the speakers program, Advisory board: AstraZeneca, Boehringer Ingelheim, BMS, Merck, Celgene, Novartis, Pfizer, Roche. R. Shiga, C.C. Lee, K. Wang: Full-time employee: Daiichi Sankyo. P.A. Jänne: Consulting fees, research funding: Acea, Astellas, AstraZeneca, Araxes, ARIAD, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Eli Lilly, Ignyta, Loxo, Merrimack, Pfizer, PUMA, Genentech; Stock: Gatekeeper; Royalties: LabCorp. All other authors have declared no conflicts of interest.
cffcb1a185b2d7d5c44e9dc785b6bb25
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Proffered Paper session III (ID 64)
- Event: ELCC 2019
- Type: Proffered Paper session
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 4/12/2019, 08:30 - 10:00, Room A
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Invited Discussant 84O, 104O and 105O (ID 677)
08:30 - 10:00 | Presenting Author(s): Pasi Antero Jänne
- Abstract
- Presentation
Abstract not provided
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